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雌激素受体β通过调节线粒体融合蛋白 2 抑制雌二醇诱导的 MCF-7 细胞增殖和迁移。

Estrogen receptor β inhibits estradiol-induced proliferation and migration of MCF-7 cells through regulation of mitofusin 2.

机构信息

Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, P.R. China.

出版信息

Int J Oncol. 2013 Jun;42(6):1993-2000. doi: 10.3892/ijo.2013.1903. Epub 2013 Apr 16.

Abstract

In the present study, we investigated whether estrogen receptor (ER) β affected the proliferation and migration of the human breast cancer cell line MCF-7 through regulation of mitofusin 2 (mfn2). A previous study reported that mfn2 may be regulated by ER through a non-classical pathway; in this pathway, the ER modulates the activities of other transcription factors by stabilizing their binding to DNA and/or recruiting coactivators to the complex. However, the previous study, unlike the study presented here, did not directly explore the interactions between ER and mfn2. Here, RT-PCR and western blot analysis were used to test the expression of mfn2 in MCF-7 cells after exposure to different doses of estradiol (E2). The ability of cells to proliferate and migrate was determined by MTT assay and a monolayer-wounding protocol, respectively. Finally, changes in MCF-7 cell biology after transfection with ERβ or mfn2 expression vectors were investigated, and the role of ERβ in mfn2 expression was also explored. Our results showed that E2 attenuated mfn2 expression in a dose-dependent manner, concomitant with the activation of proliferation and migration of MCF-7 cells. The mfn2 expression vector effectively suppressed E2-induced upregulation of PCNA and migration in MCF-7 cells. ERβ inhibited the E2-induced mfn2 downregulation that accompanied the inhibition of proliferation and migration in MCF-7 cells. Briefly, ERβ may inhibit E2-induced proliferation and migration of MCF-7 cells through regulation of mfn2.

摘要

在本研究中,我们通过调节线粒体融合蛋白 2(mfn2)研究了雌激素受体(ER)β 是否影响人乳腺癌 MCF-7 细胞系的增殖和迁移。先前的研究报道 mfn2 可能通过非经典途径受 ER 调节;在该途径中,ER 通过稳定其与 DNA 的结合并/或募集共激活因子到复合物中来调节其他转录因子的活性。然而,与本研究不同,先前的研究并未直接探索 ER 和 mfn2 之间的相互作用。在这里,我们使用 RT-PCR 和 Western blot 分析检测了 MCF-7 细胞暴露于不同剂量雌二醇(E2)后 mfn2 的表达。通过 MTT 测定和单层划痕实验分别测定细胞的增殖和迁移能力。最后,转染 ERβ 或 mfn2 表达载体后研究 MCF-7 细胞生物学的变化,并探索 ERβ 在 mfn2 表达中的作用。我们的结果表明,E2 呈剂量依赖性减弱 mfn2 的表达,同时激活 MCF-7 细胞的增殖和迁移。mfn2 表达载体有效抑制了 MCF-7 细胞中 E2 诱导的 PCNA 上调和迁移。ERβ 抑制了 E2 诱导的 mfn2 下调,同时抑制 MCF-7 细胞的增殖和迁移。简而言之,ERβ 可能通过调节 mfn2 抑制 E2 诱导的 MCF-7 细胞增殖和迁移。

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